Yes相关蛋白、细胞周期蛋白D1在宫颈癌前病变与宫颈鳞癌中的表达

目的探讨Yes相关蛋白(YAP)、细胞周期蛋白D1(Cyclin D1)在宫颈癌前病变与宫颈鳞癌中的表达。方法收集100例患者宫颈病变组织,其中宫颈鳞癌35例、CIN48例、正常宫颈组织17例,以免疫组织化学法检测以上组织标本中YAP、Cyclin D1的表达。结果宫颈鳞癌组织、宫颈上皮内瘤变(CIN)组织和正常宫颈组织中YAP阳性表达率分别为65.71%、41.67%、11.76%,Cyclin D1阳性表达率分别为60.00%、33.33%、0.00%,阳性表达率在不同组织中比较差异有统计学意义(P0.05),YAP、Cyclin D1阳性表达率宫颈鳞癌组织均高于CIN组织及正常宫颈组织(P0.05),CIN组织高于正常宫颈组织(P0.05);宫颈鳞癌临床分期III-IVYAP、Cyclin D1阳性表达率为80.00%、75.00%高于Ⅰ~Ⅱ期者46.67%、40.00%(P0.05),有淋巴结转移者YAP、Cyclin D1阳性表达率为78.26%、73.91%高于Ⅰ~Ⅱ期者41.67%、33.33%(P0.05);CINⅢ期者YAP、Cyclin D1阳性表达率为55.56%、48.15%高于Ⅱ期者23.81%、14.29%(P0.05)。结论 YAP、Cyclin D1在宫颈癌前病变与宫颈鳞癌中的表达均有上调,并与病情发生及发展密切相关。     

p27kip1蛋白在宫颈癌及癌前病变中的表达及临床意义

目的:探讨宫颈癌及癌前病变组织中p27kip1蛋白的表达情况及临床意义。方法:采用免疫组化S-P法检测32例宫颈正常鳞状上皮、70例宫颈上皮内瘤样病变(CINⅠ22,CINⅡ24,CINⅢ24)、47例宫颈浸润癌中p27kip1蛋白的表达,分析宫颈癌形成过程中p27kip1蛋白表达的变化以及p27kip1蛋白表达与宫颈癌临床病理特征的关系。结果:p27kip1蛋白在CINIII及宫颈浸润鳞癌中表达平均阳性细胞百分率分别为37.1%,14.3%,显著低于宫颈正常鳞状上皮和CINⅠ、Ⅱ(分别为58.0%,65.9%,62.1%),有统计学意义(P<0.0001)。p27kip1蛋白在不同组织类型、分化程度、临床期别、有无淋巴转移的宫颈浸润癌中的表达无统计学差异。结论:p27kip1蛋白表达下降可能在宫颈细胞的恶性转化过程中起重要作用,为宫颈癌变的早期信号。     

P16、Ki67蛋白在子宫颈上皮内瘤变中的表达及意义

目的 观察宫颈上皮内瘤变(CIN)中P16、Ki67蛋白的表达,探讨它们在宫颈不成熟鳞状上皮化生与CIN鉴别诊断中的作用.方法 应用免疫组化方法检测67例CIN和40例慢性子宫颈炎伴鳞状上皮化生中P16、Ki67蛋白表达.结果 P16蛋白阳性表达率分别为CINⅠ20例(20/22),CINⅡ 19例(19/20),CINⅢ25例(25/25);慢性炎症组9例(9/40).Ki67蛋白阳性表达率分别为CINⅠ20例(20/22),CINⅡ 19例(19/20),CINⅢ25例(25/25);慢性炎症组1例(1/40).结论 P16、Ki67联合检测可作为区分宫颈CIN与宫颈不成熟鳞状上皮化生的标记物,其表达的分层现象能够很好的反映出CIN的分级.     

HMGA1蛋白在宫颈癌及癌前病变中的表达与临床意义

目的:探讨高迁移率族蛋白A1(HMGA1)在宫颈上皮内瘤变中的表达状态。方法:选取宫颈活检病理确诊为宫颈上皮内瘤变(CIN)38例及宫颈癌标本36例,应用免疫组化SP法检测HMGA1蛋白的表达,并与正常宫颈组织进行对比研究。结果:HMGA1蛋白的阳性表达率与宫颈上皮内瘤变组织的病变程度呈正相关,在宫颈癌中高表达。结论:HMGA1蛋白可作为有价值的诊断指标应用于宫颈癌高危人群筛查。     

p27kipl蛋白在宫颈癌及癌前病变中的表达及临床意义

目的:探讨宫颈癌及癌前病变组织中p27kipl蛋白的表达情况及临床意义.方法:采用免疫组化S-P法检测32例宫颈正常鳞状上皮、70例宫颈上皮内瘤样病变(CIN Ⅰ 22, CIN Ⅱ 24, CIN Ⅲ 24)、47例宫颈浸润癌中p27kipl蛋白的表达,分析宫颈癌形成过程中p27kipl蛋白表达的变化以及p27kipl蛋白表达与宫颈癌临床病理特征的关系.结果:p27kipl蛋白在NIN 及宫颈浸润鳞癌中表达平均阳性细胞百分率分别为37.1%,14.3%,显著低于宫颈正常鳞状上皮和CIN Ⅰ、Ⅱ(分别为58.0%,65.9%,62.1%),有统计学意义(P<0.0001).p27kipl蛋白在不同组织类型、分化程度、临床期别、有无淋巴转移的宫颈浸润癌中的表达无统计学差异.结论p27kipl蛋白表达下降可能在宫颈细胞的恶性转化过程中起重要作用,为宫颈癌变的早期信号.     

宫颈鳞状上皮病变中人乳头瘤病毒L1蛋白与P16、Ki-67的表达及意义

目的:研究宫颈鳞状上皮病变中人乳头瘤病毒(HPV)L1蛋白与P16、Ki-67的表达,探讨HPV L1蛋白与P16、Ki-67在宫颈病变发展过程中的意义。方法:采用免疫组织化学(IHC)方法检测宫颈鳞状上皮病变230例〔其中尖锐湿疣50例,宫颈上皮内瘤变(CIN)Ⅰ级60例,CINⅡ~Ⅲ级95例,浸润性鳞状细胞癌25例〕中HPV L1蛋白与P16、Ki-67的表达情况,并研究其相关性。结果:宫颈鳞状上皮病变中HPV L1的阳性率为43.91%。其中在尖锐湿疣中HPV L1的阳性率为62.00%,在CINⅠ中HPV L1的阳性率为70.00%,在CINⅡ~Ⅲ中HPV L1的阳性率为29.47%,浸润性鳞状细胞癌中无表达;宫颈鳞状上皮病变中P16的阳性率为76.52%,在尖锐湿疣中P16的阳性率为30.00%,在CINⅠ中P16的阳性率为70.00%,在CINⅡ~Ⅲ中P16的阳性率为98.95%,浸润性鳞状细胞癌中P16的阳性率为100.00%;宫颈鳞状上皮病变中Ki-67的阳性率为76.08%,在尖锐湿疣中Ki-67的阳性率为28.00%,在CINⅠ中Ki-67的阳性率为68.33%,在CINⅡ~Ⅲ中Ki-67的阳性率为100.00%,浸润性鳞状细胞癌中Ki-67的阳性率为100.00%。HPV L1的阳性率随宫颈病变的发展而呈下降趋势,P16、Ki-67的阳性率则呈现升高趋势。结论:HPV L1与宫颈鳞状上皮内瘤变密切相关;抑癌基因P16蛋白的表达上调参与宫颈鳞状细胞癌的发生、发展过程;联合检测HPV L1、P16、Ki-67对宫颈上皮内瘤变的诊断及分级具有重要意义。     

脆性组胺三联体、增殖细胞核抗原蛋白与宫颈上皮内瘤变恶性程度的相关性研究

目的研究脆性组胺三联体（fragile histidine triad，FHIT）蛋白和增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）蛋白在宫颈涂片中的表达及在宫颈癌前病变诊断中的意义。方法选取2004年6月至2005年6月在兰州大学第一医院妇科门诊宫颈计算机辅助细胞学检测涂片（computer—assisted cytology test，CCT）为低度鳞状上皮内病变（low-grade squamous intraepithelial lesion，LSIL）（74例）和高度鳞状上皮内病变（high—grade squamous intraepithelial lesion，HSIL）（40例）的可疑宫颈病变患者114例，采用免疫组化法检测患者宫颈组织中脆性组胺三联体、增殖细胞核抗原蛋白的表达情况。结果脆性组胺三联体蛋白在正常宫颈上皮中表达，在宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）及宫颈癌中表达缺失，在宫颈上皮内瘤变Ⅰ、宫颈上皮内瘤变Ⅱ、宫颈上皮内瘤变Ⅲ及宫颈癌组织中，其表达缺失率分别为13．3％，30．0％，60．0％和71．4％。增殖细胞核抗原蛋白在宫颈上皮内瘤变及宫颈癌中表达升高，在宫颈上皮内瘤变Ⅰ、宫颈上皮内瘤变Ⅱ、宫颈上皮内瘤变Ⅲ及宫颈癌组织中，其阳性表达率分别为44．7％，60．0％．80．0％，85．7％，而且其染色强度明显升高。各组间脆性组胺三联体蛋白、增殖细胞核抗原蛋白表达率比较，差异有显著意义（P=0．0001）。结论脆性组胺三联体蛋白表达缺失，是宫颈癌发生的早期事件，其表达缺失程度与宫颈上皮内瘤变的分级有关，高级别的癌前病变缺失率明显增高；增殖细胞核抗原蛋白的表达，在宫颈癌前病变中逐级增高，可用于评估癌前病变的恶变潜能。     

P16与Rb蛋白在宫颈上皮癌变过程中的表达及意义

目的探讨P16与Rb蛋白在宫颈癌及癌前病变中的表达及其相互关系,以期为早期诊断及治疗宫颈癌提供理论依据.方法应用免疫组化技术(SP法),检测Rb与P16基因蛋白在20例正常宫颈组织、28例宫颈上皮内瘤样病变(CIN)及59例宫颈鳞状细胞癌组织中的表达.结果①Rb蛋白在正常宫颈、CIN、宫颈鳞癌(SCC)中阳性表达率分别为90%、71.43%、38.98%.宫颈癌与CIN及正常宫颈之间,差异有显著性(P<0.01).②P16蛋白在正常宫颈、CIN、宫颈鳞癌(SCC)中过表达率分别为25%、44%、67.24%.逐渐升高.三组之间差异有极显著性(P<0.01).③在宫颈病变组织中,P16蛋白的过表达与Rb的表达呈负相关(P<0.05).结论Rb蛋白表达阴性的癌前病变可能有较高的癌变易变性.P16蛋白的过表达在宫颈癌中是一常发事件,可将P16蛋白作为一种生物学标记物早期筛选宫颈癌.二者联合可预测宫颈癌预后.     

宫颈上皮内瘤变高危型HPV-L1壳蛋白检测的意义

目的:探讨HPVL1壳蛋白在不同宫颈病变中的表达及其临床意义并提示其预后.方法:应用赛泰试剂盒,用免疫组化方法检测不同宫颈病变中HPVL1壳蛋白的表达.结果:慢性宫颈炎和宫颈鳞状细胞癌中HPVL1壳蛋白检测阴性.HPVL1壳蛋白在CINⅠ、CINⅡ和CINⅢ级中的阳性表达率分别为79.5％、50％和12.5％,CINⅡ级中HPVL1壳蛋白表达明显低于CINⅠ;CINⅢ明显低于CINⅡ;差异有统计学意义(P＜0.01).结论:HPVL1壳蛋白的检测可预测宫颈病变的发展趋势,尤其是对CINⅠ和CINⅡ的宫颈病变的治疗具有指导价值.人乳头状瘤病毒(HPV)感染是引发宫颈癌的重要因素,但是大部分HPV感染是亚临床的、自限性的,可造成不同的子宫颈病变,并不是所有的HPV感染都会进展为宫颈癌.目前临床常用的诊断技术尚无法预测HPV感染引起子宫颈病变的转归,因而大量患者被过度治疗.HPVL1壳蛋白是近年来发现的一种反映HPV感染预后的重要生物标记物.作者应用最新引进的“赛泰”HPVL1壳蛋白检测试剂盒,采用免疫组化方法检测不同级别宫颈鳞状上皮内瘤变中HPVL1壳蛋白的表达,旨在探讨预测宫颈鳞状上皮内瘤变进展中的价值.     

宫颈癌及其癌前病变组织NET-1基因蛋白的表达及意义

目的:探讨宫颈癌及其癌前病变组织中NET-1基因蛋白的表达及意义。方法:应用免疫组化S-P法对50例宫颈鳞癌组织、36例宫颈上皮内瘤样病变(CINⅠ～Ⅲ级)及5例正常宫颈组织中的NET-1基因蛋白进行检测。结果:NET-1基因蛋白在正常宫颈组织中不表达,在CINⅢ中表达显著高于CINⅠ和CINⅡ(均P<0.01);在CINⅢ和宫颈癌中的表达阳性率分别为78.57%、76.00%,两组比较无显著差异(P>0.05);NET-1表达阳性率及阳性强度与宫颈癌淋巴结转移呈显著正相关(P<0.01)。结论:NET-1过表达可能是宫颈癌发生的早期分子事件,可作为CIN病情监测、处理的辅助指标;NET-1高表达赋予了癌细胞更显著的侵袭、转移潜能。     

Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis

BACKGROUND: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis. OBJECTIVE: We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding. DESIGN: In 8 pediatric CF patients, we administered 3 randomly allocated isocaloric diets with normal (NP), intermediate (IP), and high (HP) amounts of protein (1.5, 3, and 5 g . kg(-1) . d(-1), respectively) by continuous drip feeding during a 4-d period at 6-wk intervals. Each patient acted as his or her own control. On the fourth day of feeding, whole-body protein synthesis and breakdown were measured. RESULTS: Protein synthesis was significantly higher in the HP group (x +/- SEM: 1.78 +/- 0.07 micromol . kg(-1) . min(-1)) than in the IP (1.57 +/- 0.08 micromol . kg(-1) . min(-1); P=0.001) and NP (1.37 +/- 0.07 micromol . kg(-1) . min(-1); P < 0.001) groups. There were no significant differences in protein breakdown. Net retention of nitrogen was significantly higher in the HP group (12.93 +/- 1.42 micromol . kg(-1) . min(-1)) than in the IP (7.61 +/- 1.40 micromol . kg(-1) . min(-1); P=0.01) and HP (2.48 +/- 0.20 micromol . kg(-1) . min(-1); P < 0.001) groups. CONCLUSION: In stunted children with CF requiring tube feeding, the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1) . d(-1).     

Effects of protein and energy on dietary selection and protein utilization in rats with ventromedial hypothalamic lesions

The effect of bilateral destruction of the ventromedial hypothalamus (VMH) on protein and energy intakes was examined in relation to protein utilization. In Experiment 1, rats with VMH lesions were allowed to select protein (either casein or wheat gluten) and energy from two diets containing 70% and 5% protein, respectively. In Experiment 2, they were restricted to 0, 100 and 200 mg N/day of protein and given free access to protein-free diet. In Experiment 3, they were restricted to 2 and 5 g/day of protein-free diet but given 92% protein diet ad libitum. Self-selecting rats with VMH lesions consumed about 100 kcal/day regardless of the protein source, in contrast to sham-operated controls which consumed 75 kcal/day. They showed increased non-protein energy intake with constant protein consumption resulting in normal protein retention with increased body fat. When protein intake was restricted to 200 mg N/day, energy intake was reduced in animals given diet containing wheat gluten more than in those given diet containing casein, resulting in lower protein utilization. Therefore, food intake depended upon the amount of dietary protein. Rats with VMH lesions showed an exaggerated response to the ratio of protein to energy in the diet and consumed more energy from balanced diet but showed more reduction in food intake than controls in response to diet with an inappropriate ratio of protein to energy. The present study confirmed that the VMH was related to regulation of energy intake but not protein intake. It is suggested that protein intake is regulated in relation to maintenance of body protein in rats with VMH lesions as well as in normal rats.     

Utilization of soy protein isolate mixed with rice protein in Japanese women

Utilization and requirement of soy protein isolate (SPI) and SPI-rice combination were examined in twenty-five female students. After 1 day on protein-free diet, each subject received a low-protein diet for 10 days. The protein sources were SPI for ten subjects and SPI-rice combination, in which the ratio of two proteins was 6:4, for fifteen subjects. The nitrogen intakes were about 45, 65 and 85 mg/kg in both the two series of experiments. Energy intake was at an approximate maintenance level of 36.1 +/- 3.0 kcal/kg. Apparent nitrogen balance improved with increase in nitrogen intake. The regression equations between nitrogen intake (X, mg/kg) and balance (Y, mg/kg) are shown in the following: SPI: Y = 0.411 X - 40.8 (n = 10, r = 0.812) SPI and rice protein: Y = 0.392 X -32.7 (n = 15, r = 0.739) From the above equations, the maintenance intakes of SPI and SPI-rice combination for an apparent nitrogen equilibrium were calculated to be 99 and 83 mg N/kg, respectively. Digestibilities were 98.2 +/- 5.0% for SPI and 93.1 +/- 6.1% for SPI-rice combination. The NPUs of SPI at intake levels of 40, 60 and 80 mg N/kg were 47 +/- 24 (n = 4), 49 (n = 2) and 44 +/- 3 (n = 4), respectively. The NPUs of SPI and rice mixed protein at intake levels of 45, 70 and 90 mg N/kg were 67 +/- 13 (n = 5), 51 +/- 7 (n = 5) and 54 +/- 12 (n = 5), respectively. It was concluded from the present study that both SPI and the SPI-rice combination had a high nutritive efficiency comparable with that of egg protein.     

HDCP患者血清Apelin蛋白水平与尿蛋白定量的相关性

目的 探讨妊娠期高血压疾病(HDCP)患者血清Apelin蛋白水平与24小时尿蛋白定量的相关性.方法 选择妊娠期高血压疾病孕妇65例,其中妊娠期高血压(GH)23例,轻度子痫前期(mPE) 22例,重度子痫前期(sPE) 20例,同期正常孕妇30例为对照组,比较各组孕妇血清Apelin蛋白及24小时尿蛋白定量情况,分析其相关性.结果 GH、mPE及sPE组患者血清Apelin蛋白水平均明显低于对照组(t值分别为18.49、18.34、40.97,均P＜0.05),且sPE组明显低于mPE组(t=16.29,P＜0.05),mPE组明显低于GH组(t=8.97,P＜0.05).GH、mPE及sPE组患者24小时尿蛋白定量均明显高于对照组(t值分别为3.53、5.93、9.51,均P＜0.05).相关性分析显示,GH、mPE、sPE组患者的血清Apelin蛋白值与24小时尿蛋白定量均呈显著负相关(r值分别为-0.99、-0.92、-0.78,均P＜0.01),而对照组中两指标无明显相关性(r=0.23,P＞0.05).结论 血清Apelin蛋白与妊娠期高血压病组的尿蛋白水平相关,Apelin蛋白可能参与蛋白尿形成.     

Undernutrition in sheep. The effect of supplementation with protein on protein accretion

In a comparative-slaughter experiment, individually rationed wether lambs initially of 42 kg were given 235, 362 or 456 kJ metabolizable energy (ME)/kg live weight (LW)0.75 per d as sodium hydroxide-treated barley straw with urea (six lambs per treatment), or NaOH-treated barley straw with urea plus 125 g/d white-fish meal to give 307 or 488 kJ ME/kg LW0.75 per d (seven lambs per treatment) for 92 d. All unsupplemented lambs lost both fat and body protein. The changes in fat were -3.53, -2.75 and -1.40 (SE 0.59) kg (initial value 8.6 kg), and the changes in body protein were -0.47, -0.09 and -0.14 (SE 0.13) kg (initial value 4.9 kg) for the three unsupplemented groups respectively. When supplemented with fish meal, fat was again lost as -1.53 and -0.93 (SE 0.55) kg, but wool-free body protein was increased, and gains were 0.48 and 0.89 (SE 0.12) kg for the two supplemented groups respectively. All animals lost wool-free body energy, total changes being -150, -111, -59 and -49 and -16 MJ respectively. When corrected to an equal ME intake the supplemented lambs, when compared with the unsupplemented lambs, gained (instead of losing) body protein (P less than 0.001) and lost less fat (P less than 0.05). Wool growth did not respond to supplemental protein, but was related to ME intake with an increase of 0.78 g wool fibre for each additional MJ ME. The maintenance requirements of the unsupplemented and supplemented groups respectively were estimated by regression analysis to be 554 and 496 kJ ME/kg LW0.75 per d. The apparent utilization of ME below energy equilibrium (km) was 0.31 (SE 0.08) for the unsupplemented animals, and 0.12 (SE 0.10) for the supplemented animals, well below a km of 0.70 which current UK standards (Agricultural Research Council, 1980) would predict. Most of these differences could be reconciled if basal metabolism was assumed not to be constant. It is concluded that lambs in negative energy balance can continue lean body growth at the expense of body fat, provided sufficient dietary protein is available. It is also concluded that since the animals at the lowest ME intakes required less ME than predicted by current feeding standards, the effect was that it would have been difficult to distinguish between the apparent utilization of ME for maintenance (km) and for fattening (kf).     

Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease

BACKGROUND: It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism. OBJECTIVE: The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons. DESIGN: Eight normal-weight COPD patients and 8 healthy control subjects were examined on 2 test days. Simultaneous continuous intravenous infusion of l-[ring-(2)H(5)]phenylalanine (Phe) and l-[ring-(2)H(2)]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein.kg body weight(-1).20 min(-1)) in a crossover design. Together with the meal, oral ingestion of 1-[(13)C]Phe was performed to measure first-pass Phe splanchnic extraction (SPE(Phe)). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS - WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. RESULTS: Soy feeding induced a reduction in WbPB and an increase in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P < 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SPE(Phe) (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related reduction in splanchnic protein synthesis. CONCLUSION: BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients.     

青少年睡眠与C-反应蛋白及胰岛素代谢的相关性

目的 探讨青少年睡眠状况与C-反应蛋白(CRP)异常及高胰岛素血症的相关性,为代谢异常相关疾病的预防提供参考.方法 基于中国安徽代谢综合征研究,共选取653名12～ 19岁青少年,分析晨起时间、就寝时间、睡眠呼吸障碍(SDB)与CRP异常及高胰岛素血症之间的相关性.结果 晨起时间晚与空腹高胰岛素血症发生风险上升相关(O...